A Novel Millimeter-wave (mmw) DNP/EPR Front-end Compatible with Versatile High-field NMR Probes Abstract There has been explosive growth in interest in Dynamic Nuclear Polarization (DNP) with Magic Angle Spinning (MAS) over the past five years because it has demonstrated S/N gains exceeding two orders of magnitude at ~100 K compared to conventional MAS-NMR and non-spinning NMR of biological macromolecules in their supramolecular assemblies under ambient conditions. The reduction in signal acquisition time up to four orders is promising for a wide range of applications, and in particular structure determination and function elucidation of biological macromolecules. Despite this enormous potential benefit, the adaptation rate of DNP will be severely limited by its very high price tag (currently $2-6M), largely because of the expensive gyrotron that has been required and because of the need for a special NMR magnet with superconducting sweep coils (as the bandwidth of the gyrotron is very narrow). Our preliminary simulations of a novel millimeter wave (mmw) DNP cavity that is compatible with a new MAS spinner design have shown the potential for achieving the needed electron spin saturation with up to two orders of magnitude lower microwave power than with existing MAS-DNP probes for samples of similar volume (1-15 ?L) and other conditions. With such an advance in mmw cavity design, along with the order-of- magnitude progress in broad-band solid-state InP mmw power amplifiers seen over the past five years (amplifiers now up to 850 GHz), it can become possible to eliminate both the gyrotron and need for a special NMR magnet with superconducting sweep coils, even at NMR frequencies to 1200 MHz (800 GHz EPR). These transformational advances can permit an enormous reduction in the cost of bringing MAS-DNP into an ssNMR laboratory, thereby making it possible for virtually all current NMR groups to begin developing and applying powerful new methods to structure determination and function elucidation of insoluble rigid proteins and other macromolecules that are key to progress in developing cures for Alzheimer?s Disease and cancer. However, in addition to the need for efficient MAS-DNP mmw spinner cavities, a novel low-cost EPR mmw front-end (bridge) is critically needed so that EPR experiments can first be carried out within the high- field NMR magnet on the prepared sample to facilitate essential calibration and optimization for the subsequent MAS-DNP experiments. Unfortunately, the needed mmw front-end hardware is not available and a radically new approach appears necessary if DNP is to become widely implemented. This Phase-I would design, develop, and characterize a unique microelectronics mmw circuit for initial demonstration (during the Phase-II) at 200GHz/300MHz that will be the basis for an add-on DNP/EPR front- end accessory, eventually up to 800 GHz for existing high-field ssNMR spectrometers. Simulations, analysis, and hardware tests will establish the potential for an order of magnitude reduction in system cost and two orders of magnitude increase in EPR sensitivity compared to previously published approaches to high-field EPR. Moreover, the novel approach will be compatible with H/X/Y MAS-DNP probes of commercially viable designs.